Endothelin and its signaling - Genetic analysis in mice

Research output: Contribution to journalArticle

Abstract

Endothelins are a family of small peptide ligands (ET-, ET-2 and ET-3) that act on two G protein-coupled heptahelical receptors (ETA and ETB)- ET-1 was originally identified as a powerful vasoeonst. rictor factor derived from the vascular endothelium. Mature, 21-residue endothelins are produced from biologically inactive, 38-41 residue intermediates, termed big endothelins, via a proteolytic activation catalyzed by recently identified membrane-bound metalloproteases, endothelin converting enzyme-1 and -2 (ECE-1 and ECE-2). Deregulation of endothelins has been implicated in a number of disorders involving abnormal vascular tone. As an approach to better understanding the physiological role of the endothelin system, we have been systematically knocking out its individual molecular components in mice. Unexpected results from these gene targeting experiments have provided new insights into the important roles of endothelin pathways in development of neural crest-derived tissues. Findings in the knockout mice have directly led to the discovery that defects in the human ETB and ET-3 genes cause Hirschsprung disease (congenital megacolon) and related neurocristopathies. These findings establish endothelins as the first examples of G protein-coupled cell-cell signaling molecules that are involved in mammalian embryonic development. Also, experiments are underway utilizing these mutant mice to genetically dissect the role ofendothelins in adult vascular homeostasis, including the regulation of blood pressure. Preliminary genetic evidence suggesting the involvement of the ETB receptor in the regulation of basal blood pressure will be discussed.

Original languageEnglish (US)
JournalFASEB Journal
Volume11
Issue number9
StatePublished - 1997

Fingerprint

endothelins
Endothelins
genetic techniques and protocols
mice
Hirschsprung Disease
blood vessels
Blood pressure
Blood Vessels
GTP-Binding Proteins
Blood Pressure
blood pressure
Genes
Gene Targeting
Cell signaling
megacolon
Neural Crest
Vascular Endothelium
Metalloproteases
Endothelin-1
G-Protein-Coupled Receptors

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Endothelin and its signaling - Genetic analysis in mice. / Yanagisawa, Masashi.

In: FASEB Journal, Vol. 11, No. 9, 1997.

Research output: Contribution to journalArticle

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